Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.12.7.2 (hydrogenase)
 3,522 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrogenase enzymes are natural biocatalysts that might be harnessed to reduce the cost of hydrogen gas production. [FeFe]-hydrogenases are the most effective of three such enzymes at catalyzing H(+) reduction. In this study, we develop and apply a novel combination of all-atom molecular dynamics and coarse-grained (CG) analysis to characterize two important steps of the catalytic cycle of [FeFe]-hydrogenase. The first is the electron transport through FeS clusters to the active site. We use a Marcus formulation to compute the free energy and the reorganization energy of three electron transport steps and decompose these values into contributions from the CG protein sites and the solvent. The three-step transport process is found to be downhill with relative free energies of -11.7 for the first step, -14.8 for the second step, and -17.1 kcal/mol for the third step. The electron-transport process is also found to activate a water channel suggesting a coupled mechanism for proton and electron transport to the active site. The channel opening is orchestrated by three CG sites located in the active-site domain of the protein with one of the sites also contributing a strong attractive electrostatic potential (ESP) to help shuttle protons to the active site. Overall, our CG analysis points to a concerted mechanism of electron and proton delivery to the active site in these proteins thus providing important insight for the development of biomimetic devices.
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PMID:Unraveling the role of the protein environment for [FeFe]-hydrogenase: a new application of coarse-graining. 2348 58

Hydrogenase enzymes are important because they can reversibly catalyze the production of molecular hydrogen. Proton transport mechanisms have been previously studied in residue pathways that lead to the active site of the enzyme via residues Cys299 and Ser319. The importance of this pathway and these residues has been previously exhibited through site-specific mutations, which were shown to interrupt the enzyme activity. It has been shown recently that a separate water channel (WC2) is coupled with electron transport to the active site of the [FeFe]-hydrogenase. The water-mediated proton transport mechanisms of the enzyme in different electronic states have been studied using the multistate empirical valence bond reactive molecular dynamics method, in order to understand any role WC2 may have in facilitating the residue pathway in bringing an additional proton to the enzyme active site. In a single electronic state A(2-), a water wire was formed through which protons can be transported with a low free energy barrier. The remaining electronic states were shown, however, to be highly unfavorable to proton transport in WC2. A double amino acid substitution is predicted to obstruct proton transport in electronic state A(2-) by closing a cavity that could otherwise fill with water near the proximal Fe of the active site.
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PMID:Electron transfer activation of a second water channel for proton transport in [FeFe]-hydrogenase. 2549 98